Carbamate → HCID 69983039, compound

HRID 1167498Notes

Reaction equation

HRID 1167498 reaction equation
C(N(C(C)C)CC)(C)C.[S:10]1[N:14]=[CH:13][C:12]([O:15][CH2:16][C@@H:17]2[O:21][C:20](=[O:22])[N:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH2:34][CH2:33][N:32](CC5C=CC=CC=5)[CH2:31][CH:30]=4)=[C:25]([F:42])[CH:24]=3)[CH2:18]2)=[N:11]1.[Cl:43]C(OC(Cl)C)=O.C(=O)([O-])N.C(Cl)C1C=CC=CC=1>ClCCl>[ClH:43].[S:10]1[N:14]=[CH:13][C:12]([O:15][CH2:16][C@@H:17]2[O:21][C:20](=[O:22])[N:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH:30]=4)=[C:25]([F:42])[CH:24]=3)[CH2:18]2)=[N:11]1

Participants

7

Reactant 5

HCID 276CarbamateHCID 7503Benzyl ChlorideHCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 69979950HCID 69979950, compound

Product 1

HCID 69983039HCID 69983039, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Diisopropylethylamine (0.39 ml, 2.24 mmol) was added dropwise to a stirred solution at 5° C. under nitrogen of 5(R)-1,2,5-thiadiazol-3-yloxymethyl-3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3-fluorophenyl)oxazolidin-2-one (3.48 g, 7.47 mmol) in dichloromethane (60 ml), followed by 1-chloroethyl chloroforrnate (1.05 ml, 9.73 mmol). The mixture was stirred at 5° C. for 2 hours and the intermediate carbamate was freed from benzyl chloride by flash-column chromatography (silica gel. Merck 7736), eluting with a gradient of 10-30% EtOAc in isohexane. The carbamate was heated in refluxing MeOH (40 ml) for 1 hour. Solvent was evaporated and the residue triturated with ether to give 5(R)-1,2,5-thiadiazol-3-yloxymethyl-3-(3-fluoro-4-(1,2,5,6-tetrahydropyrid-4-yl)phenyl)oxazolidin-2-one hydrochloride as a solid in 82% yield MS: 376 (MH+)(free base); NMR; 2.67 (2H, s); 3.3 (2H+DMSO); 3.75 (2H, s); 4.0 (1H, m); 4.25 (1H, t); 4.7 (2H, m); 5.14 (1H, m); 6.05 (1H, s); 7.4 (2H, m): 7.55 (1H, d); 8.42 (1H, s); 9.35 (1H, bs).

Workup

  1. washeluting with a gradient of 10-30% EtOAc in isohexane
  2. temperatureThe carbamate was heated
  3. temperaturein refluxing MeOH (40 ml) for 1 hour
  4. customSolvent was evaporated
  5. customthe residue triturated with ether

Sources & evidence

ORD record
ord-d97e615bd9324b2ebbe2c0f83ef2a433
Source dataset
uspto-grants-2003_09
Patent number
US06617339B1

Reaction notes

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